Follow-up of 1715 SNPs from the Wellcome Trust Case Control Consortium genome-wide association study in type I diabetes families View Full Text


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Article Info

DATE

2009-12

AUTHORS

J D Cooper, N M Walker, D J Smyth, K Downes, B C Healy, J A Todd

ABSTRACT

The advent of genome-wide association (GWA) studies has revolutionized the detection of disease loci and provided abundant evidence for previously undetected disease loci that can be pooled together in meta-analysis studies or used to design follow-up studies. A total of 1715 SNPs from the Wellcome Trust Case Control Consortium GWA study of type I diabetes (T1D) were selected and a follow-up study was conducted in 1410 affected sib-pair families assembled by the Type I Diabetes Genetics Consortium. In addition to the support for previously identified loci (PTPN22/1p13; ERBB3/12q13; SH2B3/12q24; CLEC16A/16p13; UBASH3A/21q22), evidence supporting two new and distinct chromosome locations associated with T1D was observed: FHOD3/18q12 (rs2644261, P=5.9 x 10(-4)) and Xp22 (rs5979785, P=6.8 x 10(-3); http://www.T1DBase.org). There was independent support for both SNPs in a GWA meta-analysis of 7514 cases and 9045 controls (P values=5.0 x 10(-3) and 6.7 x 10(-6), respectively). The chromosome 18q12 region contains four genes, none of which are obvious functional candidate genes. In contrast, the Xp22 SNP is located 30 kb centromeric of the functional candidate genes TLR8 and TLR7 genes. Both TLR8 and TLR7 are functional candidate genes owing to their key roles as pathogen recognition receptors and, in the case of TLR7, overexpression has been associated directly with murine autoimmune disease. More... »

PAGES

s85

References to SciGraph publications

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URI

http://scigraph.springernature.com/pub.10.1038/gene.2009.97

DOI

http://dx.doi.org/10.1038/gene.2009.97

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1016202275

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19956107


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